Prognostic impact of shock in patients with type A acute aortic syndrome. Results of a nationwide multicenter study.

OBJECTIVE: To evaluate the clinical characteristics, imaging findings, treatment, and prognosis of patients with type A acute aortic syndrome (AAS-A) presenting with shock. To assess the impact of surgery on this patient population. METHODS: The study included 521 patients with A-AAS enrolled in the Spanish Registry of Acute Aortic Syndrome (RESA-III) from January 2018 to December 2019. The RESA-III is a prospective, multicenter registry that contains AAS data from 30 tertiary-care hospitals. Patients were classified into two groups according to their clinical presentation, with or without shock. Shock was defined as persistent systolic blood pressure <80 mmHg despite adequate volume resuscitation. RESULTS: 97 (18.6%) patients with A-AAS presented with shock. Clinical presentation with syncope was much more common in the Shock group (45.4% vs 10.1%, p = 0.001). Patients in the Shock group had more complications at diagnosis and before surgery: cardiac tamponade (36.2% vs 9%, p < 0.001), acute renal failure (28.9% vs 18.2%, p = 0.018), and need for orotracheal intubation (40% vs 9.1%, p < 0.001). There were no significant differences in aortic regurgitation (51.6% vs 46.7%, p = 0.396) between groups. In-hospital mortality was higher among patients with shock (48.5% vs 27.4%, p < 0.001). Surgery was associated with a significant mortality reduction both in patients with and without shock. Surgery had an independent protective effect on mortality (OR 0.03, 95% CI (0.00-0.32)). CONCLUSION: Patients with AAS-A admitted with shock have a heavily increased risk of mortality. Syncope and pericardial effusion at diagnosis are strongly associated with shock. Surgery was independently associated with a mortality reduction in patients with AAS-A and shock.

Extended septal myectomy versus alcohol septal ablation: clinical results at a national referral centre.

OBJECTIVES: Extended septal myectomy and alcohol septal ablation are 2 invasive treatments for hypertrophic obstructive cardiomyopathy. Our goal was to compare which of these techniques achieved a higher reduction in gradients, improvement in New York Heart Association (NYHA) functional class and reduction in medical treatment. METHODS: It is a single-centre observational and retrospective analysis. We used multivariable regression analyses to assess the association of ablation/myectomy with different outcomes. The odds ratio or coefficient along with the 95% confidence interval was estimated according to the group and adjusted for the corresponding preprocedural variables and EuroSCORE II. RESULTS: A total of 78 patients underwent septal myectomy, and 25 patients underwent alcohol septal ablation. Basal and Valsalva gradients after myectomy were reduced to a higher degree in comparison to ablation: 21.0 mmHg [P < 0.001, 95% confidence interval -30.7; -11.3], and 34.3 mmHg (P < 0.001, -49.1; -19.5) respectively. Those patients who received a myectomy had a lower probability of having moderate mitral regurgitation (odds ratio = 0.18, P = 0.054). Patients after septal myectomy were more likely to be NYHA functional class I (80.4%), whereas patients after ablation were more likely to be NYHA functional class III (48%). Both groups continued with beta-blocker therapy, but disopyramide could be discontinued after the myectomy in more cases (20%-36% vs 59%-1.3%; P < 0.001), and there was a tendency to discontinue calcium channel blockers (48%-16% vs 15.4-3.8%; P = 0.054). CONCLUSIONS: After adjustment using preprocedural gradients and EuroSCORE II, myectomy achieves greater reduction in left ventricular outflow tract gradients compared to septal ablation.

Machine learning-based bioimpedance assessment of knee osteoarthritis severity.

This study proposes a multiclass model to classify the severity of knee osteoarthritis (KOA) using bioimpedance measurements. The experimental setup considered three types of measurements using eight electrodes: global impedance with adjacent pattern, global impedance with opposite pattern, and direct impedance measurement, which were taken using an electronic device proposed by authors and based on the Analog Devices AD5933 impedance converter. The study comprised 37 participants, 25 with healthy knees and 13 with three different degrees of KOA. All participants performed 20 repetitions of each of the following five tasks: (i) sitting with the knee bent, (ii) sitting with the knee extended, (iii) sitting and performing successive extensions and flexions of the knee, (iv) standing, and (v) walking. Data from the 15 experimental setups (3 types of measurements×5 exercises) were used to train a multiclass random forest. The training and validation cycle was repeated 100 times using random undersampling. At each of the 100 cycles, 80% of the data were used for training and the rest for testing. The results showed that the proposed approach achieved average sensitivities and specificities of 100% for the four KOA severity grades in the extension, cyclic, and gait tasks. This suggests that the proposed method can serve as a screening tool to determine which individuals should undergo x-rays or magnetic resonance imaging for further evaluation of KOA.

Clinical and structural outcomes of neocommissural alignment in transaxillary and transcarotid transcatheter aortic valve implantation with a self-expandable transcatheter heart valve.

Objectives: This study analyzes neocommissural alignment and the clinical and hemodynamic outcomes after transaxillary and transcarotid implantation of the Acurate neo2 transcatheter heart valve. Methods: We performed a retrospective, single-center analysis of early outcomes after transaxillary and transcarotid implantation of the Acurate neo2 transcatheter heart valve. Primary outcomes were neocommisural alignment, in-hospital mortality, and valve hemodynamic performance. Commissural alignment between native and transcatheter heart valves was assessed by transesophageal echocardiogram before and after the procedure. Results: Between October 2021 and November 2022, 40 consecutive patients were treated with the Acurate neo2 through a transaxillary or transcarotid approach. Access was achieved via the left subclavian artery in 30 cases and the left common carotid artery in 10 cases, with a mean vessel diameter of 6.7 mm. Implants most commonly used were size M (37.5%), L (35%), and S (27.5%). On the basis of transesophageal echocardiogram analysis, there was no significant difference in mean commissural orientation between native (mean, 65.1°; SD, 41.3°) and neocommissures (mean, 64°; SD, 44.1°) (P = .661). Mean commissural orientation did not significantly differ between native and neocommissures (P = .661). Optimal alignment or mild commissural misalignment was achieved in 99.5% of cases. There were no cases of severe commissural misalignment. Postprocedural mean values for peak and mean gradients were 12.7 mm Hg and 5.2 mm Hg, respectively. There were 2 cases of moderate paravalvular leak and 4 cases of mild paravalvular leak. Conclusions: This patient-specific technique for transaxillary and transcarotid insertion of the Acurate neo2 delivery system prevents implantations with more than mild commissural misalignment and with a high device success rate.

A low-cost, portable, two-dimensional bioimpedance distribution estimation system based on the AD5933 impedance converter.

This study proposes a low-cost, portable, eight-channel electrical impedance tomograph based on the AD5933 impedance converter. The patterns for current injection and voltage measurement are managed by an Arduino Mega 2560 board and four 74HC4067 Texas Instruments multiplexers. Regarding the experimental results, the errors in the impedance estimates of an electrical circuit that represents a Cole model were less than 1.14% for the magnitude and 4.15% for the phase. Furthermore, the signal-to-noise ratio measured in a resistive phantom was 55.23 dB. Additional experiments consisted of placing five spheres of different size and conductivity in a saline tank, measuring their impedance through eight electrodes, and then generating impedance maps using the Electrical Impedance Tomography and Diffuse Optical Tomography Reconstruction Software (EIDORS). These maps were different for each sphere, suggesting the proposed prototype as a promising alternative for medical applications.

Aortic valve reimplantation in patients with connective tissue syndromes: A 15-year follow-up.

OBJECTIVES: The goal of this study was to analyse early- and long-term outcomes of aortic valve reimplantation (David operation) in patients with heritable thoracic aortic disease. METHODS: This is a retrospective observational analysis using data from a prospectively maintained surgical database from March 2004 to April 2021. Patients with heritable thoracic aortic disease were included in the study. RESULTS: A total of 157 patients with aortic root aneurysm with the diagnosis of heritable thoracic aortic disease received the David procedure. Marfan syndrome was found in 143 (91.1%) patients, Loeys-Dietz in 13 and Ehler-Danlos in 1 patient. The median age was 35.0 (IQR: 17.5) years and the median ascending aorta diameter in the Valsalva sinuses was 48 mm (IQR: 4). A Valsalva graft was used in 8 patients; the David V technique was performed in the rest of the cases. The median follow-up time was 7.3 years [standard deviation: 0.58, 95% confidence interval (CI): 6.12-8.05]. Only 2 patients died during the follow-up period. The overall survival was 99% (95% CI: 95%; 99%); 98% (95% CI: 92%; 99%); and 98% (95% CI: 92%; 99%) at 5, 10 and 15 years. Freedom from significant aortic regurgitation (AR> II), reintervention and postoperative type-B dissection was 90% (95% CI: 77%; 95%), 96% (95% CI: 91%; 99%) and 87% (95% CI: 68%; 95%) at 15 years, respectively. No differences were found in any outcome between Marfan syndrome and Loeys-Dietz syndrome. No statistically significant differences in survival were found when we compared expected gender- and age-specific population survival values. CONCLUSIONS: The David operation is an excellent option for the treatment of patients with heritable thoracic aortic disease and dilatated aortic root. Surgical expertise in referral centres is essential to achieve the best long-term results.

Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors.

Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines.

Potencial de reducción de emisiones y captura de carbono en bosques y sistemas agroforestales con cacao en el Pacífico colombiano / Potential for reducing emissions and carbon sequestration in forests and cocoa agroforestry systems in the Colombian Pacific

Resumen Introducción: Los bosques y sistemas agroforestales (SAF) suministran bienes y servicios ecosistémicos para la sociedad, tal como la mitigación del cambio climático. Objetivo: Se estimó el potencial de reducción de emisiones y captura de carbono en bosques y SAF con cacao de la subcuenca del río Munguidó, Colombia. Métodos: Se seleccionaron tres sistemas de uso del suelo (bosque primario, bosque secundario y SAF con cacao). Se establecieron 18 parcelas temporales de muestreo, seis por sistema, para medir los árboles (diámetro a la altura del pecho -dap ≥ 10 cm) y arbustos de cacao. Se cuantificó la biomasa aérea con ecuaciones alométricas y una fracción de carbono de 0.5. Se estimó la fijación de carbono en el bosque secundario y el SAF con cacao como la razón entre el carbono almacenado y su edad. La pérdida de carbono del bosque primario se estimó con base en la deforestación para Chocó y dicha subcuenca (0.6 y 0.3 %/año, respectivamente). Se realizó un análisis de varianza y comparación de medias LSD Fisher para determinar las diferencias en el almacenamiento y la fijación de carbono entre los usos. Resultados: El bosque primario almacenó más carbono que el bosque secundario y el SAF con cacao (190.1, 22.3 y 5.3 Mg/ha, respectivamente). La fijación de carbono del bosque secundario y el SAF con cacao no difirieron (2.23 vs 1.33 Mg/ha/año). En 20 años, el bosque primario presentaría una reducción de emisiones de 1.4-2.6 Tg CO2; y el bosque secundario y el SAF con cacao presentarían una captura de 100.8 y 30.7 Gg CO2, respectivamente. Conclusiones: En la subcuenca del río Munguidó es posible establecer proyectos para la reducción de emisiones en bosque primario y captura de carbono en bosques secundarios y SAF con cacao, con lo cual se podría emitir 1.4-2.6 millones de toneladas de CO2.

Abstract Introduction: Forests and agroforestry systems (AFS) provide ecosystem goods and services for society, such as climate change mitigation. Objective: The potential for emission reductions and carbon sequestration in forests and cocoa agroforestry systems in the Munguidó river sub-basin in Colombia was estimated. Methods: Three land use systems were selected (primary forest, secondary forest and AFS with cocoa). Eighteen temporary sampling plots were established, six per system, to measure trees (diameter at breast height -dbh ≥ 10 cm) and cocoa shrubs. Aboveground biomass was quantified with allometric equations and a carbon fraction of 0.5. Carbon fixation in secondary forest and AFS with cocoa was estimated as the ratio of carbon stored to its age. Carbon loss from primary forest was estimated based on deforestation for Chocó and that sub-basin (0.6 and 0.3 %/year, respectively). An analysis of variance and LSD Fisher mean comparison was performed to determine differences in carbon storage and carbon sequestration between uses. Results: Primary Forest stored more carbon than secondary forest and AFS with cocoa (190.1, 22.3 and 5.3 Mg/ha, respectively). The carbon fixation of secondary forest and AFS with cocoa did not differ (2.23 vs. 1.33 Mg/ha/year). In 20 years, the primary forest would present an emission reduction of 1.4-2.6 Tg CO2; and the secondary forest and the PFS with cocoa would present a sequestration of 100.8 and 30.7 Gg CO2, respectively. Conclusion: In the Munguidó river sub-basin, it is possible to establish projects for the reduction of emissions in primary forest and carbon sequestration in secondary forests and AFS with cocoa, which could emit 1.4-2.6 million tons of CO2.

Emergency surgical retrieval of a migrated LAmbre device through the mitral valve.

Left atrial appendage occlusion has become an alternative for long-term anticoagulation for patients with non-valvular atrial fibrillation. Although the procedure is safe, life-threatening complications such as embolization of the device or cardiac tamponade might occur. We present a case of a LAmbre device that migrated 4 days after being implanted and remained trapped in the mitral valve. Secondary massive mitral regurgitation with severe stenosis and haemodynamic instability required emergency surgery. The device was successfully removed, but severe damage in the anterior leaflet and chords forced a valve replacement.

Non-contrast transoesophageal echo-guided transapical transcatheter aortic valve replacement: 10-year experience of a renoprotective strategy.

OBJECTIVES: This study aims to evaluate the efficacy, safety and long-term outcomes of a renoprotective non-contrast, transoesophageal echocardiography-guided transapical (TA) transcatheter aortic valve replacement (TAVR) strategy with a balloon-expandable prosthesis, as well as to determine its impact on renal function. METHODS: Between 2009 and 2019, 200 consecutive patients underwent a non-contrast, transoesophageal echocardiography-guided TA TAVR with a balloon-expandable prosthesis. RESULTS: The device success rate was 95.5%. Transoesophageal echocardiography-guided deployment demonstrated a low rate of procedure-related complications: 9.5% of acute kidney injury, 8% postoperative bleeding, 6% low-cardiac output, 4.5% postprocedural aortic regurgitation ≥+2, 4% implantation of permanent pacemaker and 2% stroke. There were no significant differences between preoperative and on discharge estimated glomerular filtration rate (53.9 ± 22.2 vs 54.3 ± 22.9 ml/min/1.73 m2, P = 0.60). Logistic regression analysis confirmed postoperative bleeding as an independent predictor for acute kidney injury (odds ratio (OR) 11.148, 95% confidence interval 3.537-35.140, P < 0.001). In-hospital mortality was 7.5%. The mean follow-up was 48.5 ± 39.9 months. Renal function and patient's chronic kidney disease stage did not significantly vary during follow-up. Long-term cumulative survival at 1, 5 and 10 years was 84.2 ± 0.027%, 42.9 ± 0.038% and 32.5 ± 0.044%, respectively. Renal function affected on neither in-hospital mortality nor long-term survival. CONCLUSIONS: Non-contrast, transoesophageal echocardiography-guided TA TAVR is a safe and reproducible technique with a low incidence of periprocedural complications that avoids the use of contrast and mitigates the incidence of acute kidney injury.

Balloon-expanding transcatheter aortic valve implantation for degenerated Mitroflow bioprostheses: clinical and echocardiographic long-term outcomes.

OBJECTIVES: This study aims to analyse the risks associated with valve-in-valve procedures for treating structural valve deterioration in Mitroflow bioprostheses, as well as to determine the impact of the original Mitroflow size on the patients' long-term outcomes. METHODS: Between January 2012 and September 2019, 21 patients (61.9% males; mean age 82.4 ± 5.4 years) were treated for Mitroflow deterioration with valve-in-valve procedures (12 transapical and 9 transfemoral). RESULTS: Mean EuroSCORE I and EuroSCORE II were 28.2% ± 13.6% and 10.5% ± 6.1%, respectively. Six patients presented an indexed aortic root diameter <14 mm/m2 and 7 patients a diameter of sinus of Valsalva <30 mm. Implanted transcatheter valve sizes were 20 mm in 6 cases, 23 mm in 14 cases and 26 mm in 1 patient. A Valve Academic Research Consortium-2 complication occurred in 23.8% of cases, including 3 coronary occlusions. In-hospital mortality was 9.5%. The 20 mm transcatheter valves presented significantly higher postoperative peak and mean aortic gradients than other sizes (54.1 ± 11.3 mmHg vs 29.9 ± 9.6 mmHg, P = 0.003; and 29.3 ± 7.7 mmHg vs 17.4 ± 5.9 mmHg, P = 0.015, respectively). There were 12 cases of patient-prosthesis mismatch (57.1%) and 3 cases (14.3%) of severe patient-prosthesis mismatch. Cumulative survival was 85.7% ± 7.6% at 1 year, 74.3% ± 10% at 2 years and 37.1% ± 14.1% at 5 years. CONCLUSIONS: Valve-in-valve procedures with balloon-expandable transcatheter valves associate a high risk of coronary occlusion in patients with indexed aortic root diameter <14 mm/m2 and low coronary ostia <12 mm. Valve-in valve procedures with 20 mm balloon-expandable transcatheter valves in ≤21 mm Mitroflow bioprosthesis leave significant residual transvalvular gradients that might obscure patients' long-term outcomes.

Are 18F-fluorodeoxyglucose positron emission tomography results reliable in patients with ascending aortic grafts? A prospective study in non-infected patients.

OBJECTIVES: Our goal was to define characteristic patterns of 18F-fluorodeoxyglucose in non-infected patients with ascending aortic prosthetic grafts during the first year after surgery. METHODS: 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) was performed at 3, 6 and 12 months postoperatively in 26 uninfected patients. Clinical, analytical and microbiological (blood culture) assessments were performed to confirm the absence of infection. FDG uptake intensity [measured through maximum standardized uptake values (SUVmax) and the target-to-background ratio] and distribution patterns were obtained. Models of generalized estimating equations were used to assess the evolution of the SUVmax over time. The results were compared to those in our endocarditis-over-ascending-aortic-graft series database. The receiver operating characteristic curves of the control group and the 12-month group were assessed. RESULTS: All patients showed increased uptake in all areas. The uptake pattern was heterogeneous in 47.4%, 43.5% and 42.3% at 3, 6 and 12 months. The means and standard deviations of the SUVmax in the graft were 4.80 (±0.99), 4.28 (±0.88) and 4.14 (±0.87) at 3, 6 and 12 months after surgery. A comparison of all values obtained in the 6th and 12th months compared to those from the 3rd month revealed a slow decrease that may persist after the first year. The cut-off value of SUVmax of 4.24 had an overall sensitivity of 84.6% and specificity of 57.7% for patients seen at 12 months. CONCLUSIONS: Non-infected ascending aortic grafts showed no predominant uptake pattern; they also showed increased 18F-fluorodeoxyglucose activity that could persist beyond the first year. Caution is therefore recommended when interpreting PET/CT images obtained during the first year after surgery.

Composición florística, estructura y diversidad del bosque pluvial tropical de la subcuenca del río Munguidó, Quibdó, Chocó, Colombia / Floristic composition, structure and diversity of the tropical pluvial forest of the sub-basin of the Munguidó River, Quibdó, Chocó, Colombia / Composição florística, estrutura e diversidade da floresta pluvial tropical da sub-bacia do rio Munguidó, Quibdó, Chocó, Colômbia

RESUMEN Se caracterizó la composición florística, estructura horizontal y diversidad del bosque primario de la subcuenca del río Munguidó, Chocó, Colombia. Se estableció una parcela de muestreo de 1000 x 1000 m en donde se marcaron cuatro parcelas temporales de muestreo (PTM) de 500 x 10 m. En estas PTM se registraron los individuos con diámetro a la altura del pecho ≥ 10 cm. Se calculó el índice de valor de importancia (IVI) con base en la abundancia, dominancia y frecuencia relativas. Se encontró una abundancia promedio de 441 individuos/ha, pertenecientes a 71 especies de 63 géneros y 32 familias. Las familias mejor representadas fueron: Moraceae, Faboideae y Apocinaceae. Las especies de mayor importancia ecológica, según IVI, fueron: Virola reiidi, Chrysophyllum argenteum y Protium veneralense. El bosque de estudio presentó una alta diversidad de especies, con valores en los índices de Equidad de Shannon, Dominancia de Simpson y Diversidad de Margalef 3,6, 0,03 y 10,3, respectivamente. Este ecosistema se caracteriza por poseer una alta riqueza y diversidad de especies y poca presencia de individuos de la familia Arecaceae.

ABSTRACT The floristic composition, horizontal structure and diversity of the primary forest of the sub-basin of the Munguidó river, Chocó, Colombia were characterized. A sampling plot of 1000 x 1000 m was established, where four temporal sampling plots (TSP) of 500 x 10 m. In these TSP, the individuals with diameter at breast height equal or greater than 10 cm were registered. The importance value index (IVI) was calculated based on relative abundance, dominance and frequency. It was found a mean abundance of 441 individuals/ha, belonging to 71 species of 63 genera and 32 families. The best represented families were: Moraceae, Faboideae and Apocinaceae. The species with the greatest ecological importance, according their IVI, were: Virola reiidi, Chrysophyllum argenteum y Protium veneralense. The studied forest had a high diversity of species, with values of the indexes of Shannon Equity, Simpson Dominance and Margalef Diversity of 3.6, 0.03 and 10.3, respectively. This ecosystem is characterized by having a high richness and diversity of species and little presence of individuals of the Arecaceae family.

RESUMO A composição florística, estrutura horizontal e diversidade da floresta primária da sub-bacia do rio Munguidó, Chocó, Colômbia, foi caracterizada. Foi estabelecida uma parcela de amostragem de 1000 x 1000 m onde foram marcados quatro parcelas de amostragem temporárias (TSPs) de 500 x 10 m. Nestes TMPs, foram registrados indivíduos com diâmetro à altura do peito ≥ 10 cm. O índice de valor de importância (IVI) foi calculado com base na abundância relativa, dominância e frequência. Foi encontrada uma abundância média de 441 indivíduos/ ha, pertencentes a 71 espécies de 63 gêneros e 32 famílias. As famílias mais representadas foram: Moraceae, Faboideae e Apocinaceae. As espécies de maior importância ecológica, segundo o IVI, foram: Virola reiidi, Chrysophyllum argenteum e Protium veneralense. O estudo florestal apresentou uma alta diversidade de espécies, com valores nos índices de Shannon Equity, Simpson Dominance e Margalef Diversity 3,6, 0,03 e 10,3, respectivamente. Este ecossistema é caracterizado por uma alta riqueza e diversidade de espécies e uma baixa presença de indivíduos da família Arecaceae.

Triggered RNAi Therapy Using Metal Inorganic Nanovectors.

The administration of small interfering RNA (siRNA) is a very interesting therapeutic option to treat genetic diseases such as Alzheimer's or some types of cancer, but its effective delivery still remains a challenge. Herein, Au nanorod (GNR)-based platforms functionalized with polyelectrolyte layers were developed and analyzed as potential siRNA nanocarriers. The polymeric layers were successfully assembled on the particle surfaces by means of the layer-by-layer assembly technique through the alternating deposition of oppositely charged poly(styrene)sulfonate, PSS, poly(lysine), PLL, and siRNA biopolymers, with a final hyaluronic acid layer in order to provide the nanoconstructs with a potential targeting ability as well as colloidal stability in physiological medium. Once the hybrid nanocarriers were obtained, the cargo release, their colloidal stability in physiological-relevant media, cytotoxicity, cellular internalization and uptake, and knockdown activity were studied. The present hybrid particles release the genetic material inside cells by means of a protease-assisted and/or a light-triggered release mechanism in order to control the delivery of the oligonucleotides on demand. In addition, the hybrid nanovectors were observed to be nontoxic to cells and could efficiently deliver the genetic material in the cell cytoplasms. The GNR-based nanocarriers proposed here can provide a suitable environment to load and protect a sufficient amount of the genetic material to allow an efficient and sustained knockdown gene expression for long (up to 93% for 72 h), thanks to the slow degradation of PLL, without the observation of adverse side toxic effects. It was also found that the silencing activity was enhanced with the number of siRNA layers assembled in the nanoplatforms.

Gold Nanorod-Based Nanohybrids for Combinatorial Therapeutics.

In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2/HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules. To do that, DOXO could be successfully loaded onto the hybrid nanoconstructs through electrostatic interactions with high efficiencies of up to ca. 78.3 ± 6.9% for the first formed drug layer and 56 ± 13% for the second one, with a total efficiency for the whole system [(PSS/DOXO/PLL)2/HA-coated NRs] of ca. 65.7 ± 1.4%. Nanohybrid internalization was observed to be enhanced by the outer HA layer, which is able to target the CD44 receptors widely overexpressed in some types of cancers as lung, breast, or ovarian ones. Hence, these nanohybrid systems might be versatile nanoplatforms to simultaneously deliver sufficient heat for therapeutic plasmonic hyperthermia and the anticancer drug. Two controlled mechanisms were proposed to modulate the release of the chemodrug, one by means of the enzymatic degradable character of the PLL layer and another by the modulation of the interactions between the polymeric layers through the exploitation of the optical properties of the hybrid particles under near infrared (NIR) laser irradiation. The combination of this bimodal therapeutic approach exerted a synergistic cytotoxic effect on both HeLa and MDA-MB-231 cancer cells in vitro. Cell death mechanisms were also analyzed, elucidating that plasmonic photothermal therapy induces cell necrosis, whereas DOXO activates the cell apoptotic pathway. Therefore, the present NIR laser-induced targeted cancer thermo/chemotherapy represents a novel targeted anticancer strategy with easy control on demand and suitable therapeutic efficacy.

Efficacy and safety of transcatheter valve-in-valve replacement for Mitroflow bioprosthetic valve dysfunction.

OBJECTIVES: Bioprostheses with pericardial leaflets mounted externally on the stent pose a high risk for valve-in-valve (ViV) procedures. This study analyzed the efficacy and safety of ViV procedures for treating structural valve deterioration (SVD) in Mitroflow bioprostheses. METHODS: Between January 2012 and August 2017, 11 patients (mean age 80.3 ± 5.6 years) were treated for SVD of Mitroflow bioprostheses with transcatheter ViV procedures (six transapical [TA] and five transfemoral [TF]) using balloon expandable bioprostheses. RESULTS: All patients but one were in NYHA class III-IV. Mean STS PROM, euroSCORE I, and euroSCORE II were 8 ± 6.5%, 27.8 ± 11.5%, and 12 ± 5.9%, respectively. Two patients had a "porcelain aorta." The size of implanted valves were 23 mm in 10 cases and 26 mm in one case. One patient suffered a coronary occlusion during a TF approach. The mean volume of contrast used in TF implants was 163 ± 69.8 mL. No contrast media were used in TA procedures. There was one in-hospital death (10%). At 1 year of follow-up, peak and mean aortic gradients were 25.5 ± 5.8 mmHg and 15.5 ± 5.7 mmHg, respectively. One patient had mild paravalvular regurgitation. Cumulative survival was 90.9% at 1 year, 70.7% at 2 years, and 53% at 3 years. CONCLUSIONS: ViV procedures with balloon-expandable aortic valves provide good hemodynamic and clinical mid-term results for treating patients with a degenerated Mitroflow aortic bioprosthesis. Special care must be taken in small aortic roots, when the stented valve is in the supra-annular position to avoid coronary ostial obstruction.

Evolution of conservative treatment of acute traumatic aortic injuries: lights and shadows.

OBJECTIVES: The objective of this study is to compare early and long-term results in terms of survival and aortic complications for traumatic aortic injuries depending on the initial management strategy. METHODS: From January 1980 to January 2017, 101 patients with aortic injuries were divided into 3 groups according to management strategy at admission: 60 patients, conservative management; 26 patients, open surgery and 15 patients, endovascular repair. The groups were similar in terms of gender and trauma severity scores. RESULTS: All but 1 aortic-related complications and aortic-related mortality occurred in the conservative group (11.6% conservative vs 2.4% in both surgical and endovascular groups, P = 0.091). Total follow-up was 1109.27 patient-years. Survival in the conservative, surgical and endovascular group was 71.7%, 80.8% and 79.4% at 1 year, 68.2%, 80.8% and 79.4% at 5 years and 63.9%, 72.7% and 79.4% at 10 years, respectively (log-rank = 0.218). The rate of aortic-related complications was 58.3% in the conservative cohort. Cox regression identified the following risk factors for aortic-related complications: aortic injuries grade >I [odds ratio (OR), 3.05; P = 0.021], Trauma Injury Severity Score >50% (OR 1.21; P = 0.042) and the decade of treatment (OR 0.49; P = 0.011). CONCLUSIONS: Minimal aortic injuries seem to be an amenable target for medical management, but patients remain at risk of developing aortic-related complications. Close, long-term imaging surveillance is mandatory to detect such complications at an early stage.

Characterization of the complexation phenomenon and biological activity in vitro of polyplexes based on Tetronic T901 and DNA.

The complexation process and underlying mechanisms that rule the interaction of DNA with the cationic block copolymer Tetronic T901 to form polyplexes and their potential transfection efficiency have been studied under different solution conditions. We noted that T901 favors the formation of self-assembled structures with partially condensed DNA at smaller polymer concentrations than other Pluronic™/Tetronic™-type copolymers previously analysed. The observed polyplexes display sizes from the nano- to the micro- range as derived from DLS, electronic and optical microscopies. Also, copolymer micelles are observed at concentrations below the copolymer critical micellar concentration (cmc) induced by the presence of DNA. The complexation process is dependent on solution conditions, with electrostatic and ionic interactions being more important at acidic pH thanks to the predominant diprotonated form of the block copolymer which is less aggregation-prone, whilst dispersive forces are increasingly enhanced under basic conditions or when rising the solution temperature. Whatever the case, the complexation is mainly governed by entropic contributions, as denoted from ITC data. In vitro transfection experiments after complexing T901 with a pDNA encoding the expression of green fluorescein protein, GFP, show a relative successful fluorescence of transfected HeLa cells, which confirms the uptake, internalization and release of the genetic material within the cells at suitable [N]/[P] ratios with relatively low cytotoxicity. Despite the observed successful outcomes, the obtained transfection efficacies are slightly lower than those obtained with Lipofectamine2000, so further optimization of the polyplex formation conditions is envisaged in future studies.

Value of the coronary artery disease consortium rule in patients with acute chest pain and negative troponins referred for exercise stress testing.

OBJECTIVE: To assess the value of the pretest probability (PTP) of coronary artery disease (CAD) for predicting stress testing results and coronary events in patients with acute chest pain and negative troponins. PATIENTS AND METHODS: A total of 3527 patients without a history of CAD referred to our chest pain unit with suspected acute coronary syndromes, nondiagnostic ECGs, and negative troponin levels underwent exercise stress testing. PTP was estimated with the CAD consortium prediction rule, and was categorized as low (<15%), low-intermediate (15-65%), intermediate-high (66-85%), and high (>85%). The endpoints were the presence of signs of inducible myocardial ischemia on stress testing and the occurrence of coronary events within 6 months. RESULTS: The probability of exercise-induced myocardial ischemia was 2.6, 12.6, 42.9, and 82.1% in patients with low, low-intermediate, intermediate-high, and high PTP, respectively (Ptrend<0.001). The cumulative rate of coronary events within 6 months was also significantly lower in patients with low PTP of CAD (0.8%) than in those with low-intermediate (6.9%), intermediate-high (32.5%), or high PTP (66.7%) (Ptrend<0.001). Per 10% increment in PTP of CAD, the adjusted odds ratios for inducible myocardial ischemia and coronary events within 6 months were, respectively, 1.71 (95% confidence interval: 1.61-1.85) and 1.87 (95% confidence interval: 1.74-2.01). CONCLUSION: PTP was associated strongly with the likelihood of exercise-induced myocardial ischemia and coronary events in patients with suspected acute coronary syndromes and negative troponins. The yield of stress testing in the subset of patients with low PTP was very low.

Diagnosis, management and mortality in acute aortic syndrome: results of the Spanish Registry of Acute Aortic Syndrome (RESA-II).

BACKGROUND: Recent advances in the diagnosis and treatment of acute aortic syndrome should improve the outcome of this disease. The Spanish Registry of Acute Aortic Syndrome aimed to assess current results in acute aortic syndrome management in a wide cohort of hospitals in the same geographical area. METHODS: From January 2012 to January 2014, 26 tertiary hospitals included 629 consecutive patients with acute aortic syndrome: 73% men, mean age 64.7±14 years (range 22-92), 443 type A (70.4%) and 186 type B (29.6%). RESULTS: Time elapsed between symptom onset and diagnosis was <12 hours in 70.7% of cases and <24 hours in 84.0% (median 5 hours; 25th-75th percentiles, 2.7-15.5 hours). Computed tomography was the first diagnostic technique in 78% of patients and transthoracic echocardiography in 15%. Surgical treatment was indicated in 78.3% of type A acute aortic syndrome. The interval between diagnosis and surgery was 4.8 hours (quartile 1-3, 2.5-11.4 hours). Among the patients with type B acute aortic syndrome, treatment was medical in 116 cases (62.4%), endovascular in 61 (32.8%) and surgical in nine (4.8%). Type A mortality during hospitalisation was 25.1% in patients treated surgically and 68% in those treated medically. Mortality in type B was 13.8% in those with medical treatment, 18.0% with endovascular therapy and 33.0% with surgical treatment. CONCLUSION: Improvements in the diagnosis and treatment of acute aortic syndrome have not resulted in a significant reduction in hospital mortality. The results of this study reflect more overall and less selected information on acute aortic syndrome management and the need for sustained advances in the therapeutic strategy of acute aortic syndrome.