Aortic valve Replacement compared to Transcatheter Implant and its relationship with COgnitive Impairment (ARTICO) evaluated with neuropsychological and advanced neuroimaging: a longitudinal cohort study.

BACKGROUND: Aortic stenosis is the most common valvulopathy in Western countries. The treatment of choice had been surgery aortic valve replacement (SAVR), but the improvement in endovascular approaches as transcatheter aortic valve implantation (TAVI), initially reserved for patients with very high surgical risk, has been extended to high and intermediate, and recently also to low-risk patients. Stroke and vascular cognitive impairment are the most important complications. It is not entirely clear which technique is best to avoid these complications as well as their impact. Our goal is to evaluate changes in cognitive performance in the early (1-month) and late (1-year) postoperative period in patients undergoing SAVR or TAVI, by extensive neuropsychological study (NRP) and advanced Magnetic Resonance Imaging (MRI). Specifically, to compare early and late cognitive changes after the intervention between both groups, the occurrence of stroke during follow-up and to compare the appearance of silent vascular lesions and changes in brain activity and functional connectivity with functional MRI during follow-up between both groups. METHODS/DESIGN: Prospective longitudinal cohort study. A non-selected representative sample of 80 subjects, 40 SAVR and 40 TAVI to obtain a final sample of 36 eligible subjects in each group, ranging from 70 to 85 years old, with indication for aortic replacement and intermediate or high surgical risk will be studied. At baseline, within one month before the treatment, all individuals will undergo an extensive NRP and advanced MRI study. These studies will also be performed 1-month and 1-year after treatment, to assess the appearance of new vascular lesions, as well as changes in cognitive performance with respect to baseline. DISCUSSION: This study aims to evaluate changes in cognitive performance as well as both clinical and silent vascular events occurring in the early (1-month) and late (1-year) periods after SAVR and TAVI. We will also analyze the correlation between neuropsychological and neuroimaging approaches in order to evaluate cognition. Therefore, it may provide high-quality data of cognitive changes and vascular events for both techniques, and be useful to tailor interventions to individual characteristics and ultimately aiding in decision-making. TRIAL REGISTRATION: This study is register in Clinicaltrials.gov (NCT05235529) on 11th February 2022.

Potentiometric Study of Carbon Nanotube/Surfactant Interactions by Ion-Selective Electrodes. Driving Forces in the Adsorption and Dispersion Processes.

The interaction (adsorption process) of commercial ionic surfactants with non-functionalized and functionalized carbon nanotubes (CNTs) has been studied by potentiometric measurements based on the use of ion-selective electrodes. The goal of this work was to investigate the role of the CNTs' charge and structure in the CNT/surfactant interactions. Non-functionalized single- (SWCNT) and multi-walled carbon nanotubes (MWCNT), and amine functionalized SWCNT were used. The influence of the surfactant architecture on the CNT/surfactant interactions was also studied. Surfactants with different charge and hydrophobic tail length (sodium dodecyl sulfate (SDS), octyltrimethyl ammonium bromide (OTAB), dodecyltrimethyl ammonium bromide (DoTAB) and hexadecyltrimethyl ammonium bromide (CTAB)) were studied. According to the results, the adsorption process shows a cooperative character, with the hydrophobic interaction contribution playing a key role. This is made evident by the correlation between the free surfactant concentration (at a fixed [CNT]) and the critical micellar concentration, cmc, found for all the CNTs and surfactants investigated. The electrostatic interactions mainly determine the CNT dispersion, although hydrophobic interactions also contribute to this process.

Rational and design of the Baseline Interatrial block and Transcatheter aortic valve implantation (BIT) registry.

BACKGROUND: Aortic stenosis (AS) is currently the most frequent heart valve disease. Symptomatic severe AS has a poor prognosis and transcatheter aortic valve implantation (TAVI) is becoming the therapy of choice in these patients. Changes in the conduction tissue after the procedure constitute one of the main limitations of TAVI, with a frequent need for a definitive pacemaker. Interatrial block (IAB) is defined as a prolonged P-wave duration and is related with atrial fibrosis. The presence of IAB could be a marker of conduction tissue abnormalities at other levels. No study has specifically analyzed the role of IAB as a predictor of the need for permanent pacemaker in patients with AS undergoing TAVI. METHODS: The Baseline Interatrial block and Transcatheter aortic valve implantation (BIT) registry will be performed in approximately 3000 patients with severe AS treated with TAVI. A centralized analysis of baseline ECGs will study the presence and type of IAB and other ECG data (rhythm, P-wave duration, PR and QRS intervals/intraventricular conduction disorders). Clinical follow-up will be carried out by local researchers. The primary endpoint will be the requirement of permanent pacemaker during post-TAVI hospitalization. As secondary objectives, the incidence of new onset AF, stroke, or mortality during follow-up will be analyzed. Secondary endpoints will include the incidence of new onset AF, stroke, or mortality during follow-up. CONCLUSION: The BIT registry will study, for the first time, the influence of previous IAB in the need of permanent pacemaker after TAVI: This large registry will also provide information regarding the association of this and other ECG parameters with prognosis.

Management of Nonagenarian Patients With Severe Aortic Stenosis: The Role of Comorbidity.

BACKGROUND: The number of nonagenarian patients with aortic stenosis will likely increase due to the ageing population. We assessed the clinical characteristics, management, and outcomes of nonagenarian patients with severe aortic stenosis. METHODS: A total of 177 (117 females and 60 males) consecutive nonagenarian patients from two large contemporary registries were included in this study. Clinical characteristics, comorbidity as assessed by the Charlson Index, clinical management, and outcomes were recorded. The main outcome measure was 1-year mortality. RESULTS: The mean patient age was 91.1 years, and 56 patients (31.6%) had a Charlson Index <3. A strong association between comorbidity and 1-year overall mortality was observed, with higher 1-year mortality in patients with Charlson Index ≥3 (66.4% vs. 32.1%, p<0.001). A total of 150 patients (84.7%) were managed conservatively, and 27 (15.3%) underwent transcatheter aortic valve implantation (TAVI). Predictors of a conservative management were treatment out of TAVI centres, lower mean aortic gradient and better functional class. Clinical management was not significantly different with different degrees of comorbidity. A trend toward higher mortality in patients undergoing conservative management was observed (58% vs. 40.7%, p=0.097). Independent predictors of mortality were higher Charlson Index, lower creatinine clearance, lower mean aortic gradient, poorer left ventricular ejection fraction, significant mitral regurgitation and conservative management. CONCLUSIONS: About one third of nonagenarians with severe aortic stenosis have few comorbidities. The clinical management was similar irrespective of the Charlson Index. Both higher Charlson Index values and a conservative management were independently associated with a higher mortality.

Biocompatible metal-organic frameworks as promising platforms to eradicate HIV reservoirs ex vivo in people living with HIV.

The HIV attacks the immune system provoking an infection that is considered a global health challenge. Despite antiretroviral treatments being effective in reducing the plasma viral load in the blood to undetectable levels in people living with HIV (PLWH), the disease is not cured and has become chronic. This happens because of the existence of anatomical and cellular viral reservoirs, mainly located in the lymph nodes and gastrointestinal tract, which are composed of infected CD4+ T cells with a resting memory phenotype and inaccessible to antiretroviral therapy. Herein, a new therapeutic strategy based on nanotechnology is presented. Different combinations of antiretroviral drugs (bictegravir/tenofovir/emtricitabine and nevirapine/tenofovir/emtricitabine) and toll-like receptor agonists were encapsulated into metal-organic frameworks (MOFs) PCN-224 and ZIF-8. The encapsulation efficiencies of all the drugs, as well as their release rate from the carriers, were measured. In vitro studies about the cell viability, the hemocompatibility, and the platelet aggregation of the MOFs were carried out. Epifluorescence microscopy assays confirmed the ability of ZIF-8 to target a carboxyfluorescein probe inside HeLa cell lines and PBMCs. These results pave the way for the use of these structures to eliminate latent HIV reservoirs from anatomical compartments through the activation of innate immune cells, and a higher efficacy of the triplet combinations of antiretroviral drugs.

Single -and Multi-Walled Carbon Nanotubes as Nanocarriers for the Delivery of 7-Hydroxyflavone.

The research on flavonoids has exponentially grown since their first therapeutic evidence, in 1937. They are effective in vitro in a wide range of human diseases, particularly those mediated by free radicals, such as cancer, atherosclerosis, AIDS, or neuronal diseases. However, their applications have been reduced due to their low solubility, poor absorption, and rapid metabolism. Flavonoid encapsulation in nanocarriers significantly improves their oral absorption, protects the drug against degradation, decreases the first-pass hepatic effect, and makes absorption through the lymphatic system easier. In this work, carbon nanotubes were used as nanocarriers of 7-hydroxyflavone, 7-HF. The encapsulation of 7-HF into pristine single- and multi-walled carbon nanotubes, and into -COOH functionalized single-walled carbon nanotubes has been investigated. The equilibrium association constants were estimated. The structural backbone of 7-HF, two benzene rings linked through three carbon atoms that form a pyran heterocyclic ring containing a keto group, seems to play a key role in the 7-HF/CNT interactions, although other types of interactions are also at work. The in vitro release of 7-HF was studied at three pHs, 2.0, 7.4, and 9.2, mimicking the different biological barriers of the human organism.

Multivalent Calixarene-Based Liposomes as Platforms for Gene and Drug Delivery.

The formation of calixarene-based liposomes was investigated, and the characterization of these nanostructures was carried out using several techniques. Four amphiphilic calixarenes were used. The length of the hydrophobic chains attached to the lower rim as well as the nature of the polar group present in the upper rim of the calixarenes were varied. The lipid bilayer was formed with one calixarene and with the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, DOPE. The cytotoxicity of the liposomes for various cell lines was also studied. From the results obtained, the liposomes formed with the least cytotoxic calixarene, (TEAC12)4, were used as nanocarriers of both nucleic acids and the antineoplastic drug doxorubicin, DOX. Results showed that (TEAC12)4/DOPE/p-EGFP-C1 lipoplexes, of a given composition, can transfect the genetic material, although the transfection efficiency substantially increases in the presence of an additional amount of DOPE as coadjuvant. On the other hand, the (TEAC12)4/DOPE liposomes present a high doxorubicin encapsulation efficiency, and a slow controlled release, which could diminish the side effects of the drug.

Microheterogeneous catalysis.

The catalytic effect of micelles, polymers (such as DNA, polypeptides) and nanoparticles, saturable receptors (cyclodextrins and calixarenes) and more complex systems (mixing some of the above mentioned catalysts) have been reviewed. In these microheterogeneous systems the observed changes in the rate constants have been rationalized using the Pseudophase Model. This model produces equations that can be derived from the Brönsted equation, which is the basis for a more general formulation of catalytic effects, including electrocatalysis. When, in the catalyzed reaction one of the reactants is in the excited state, the applicability (at least formally) of the Pseudophase Model occurs only in two limiting situations: the lifetime of the fluorophore and the distributions of the quencher and the probe are the main properties that define the different situations.

FRAIL Scale also Predicts Long-Term Outcomes in Older Patients With Acute Coronary Syndromes.

OBJECTIVES: No previous studies have assessed the role of the FRAIL scale in predicting long-term outcomes in older patients with acute coronary syndromes (ACS). DESIGN, SETTING AND PARTICIPANTS: The multicenter observational LONGEVO-SCA registry included unselected patients ≥80 years of age with ACS from 44 centers. A comprehensive geriatric assessment was performed during hospitalization. MEASURES: Frailty was measured by the FRAIL scale. For the purpose of this study, main outcome measured was mortality or readmission at 24 months. RESULTS: A total of 498 patients were included. Mean age was 84.3 years. A total of 198 patients (33.1%) were prefrail and 135 (27.1%) frail. Patients who were prefrail and frail had a higher degree of comorbidities, and higher prevalence of disability, cognitive impairment, and nutritional risk. A total of 165 out of 498 patients (33.1%) died, and 331 patients (66.7%) died or were readmitted at 24 months. Both prefrailty and frailty were associated with a higher mortality compared with robust patients (P < .001). The incidence of mortality or readmission was also higher in patients who were prefrail or frail (P < .001). After adjusting for potential confounders, the association between frailty and mortality or readmission remained significant (hazard ratio 1.28 for prefrailty and hazard ratio 1.96 for frailty, P < .001). The FRAIL scale showed an optimal ability for predicting mortality or readmission (area under the receiver operating characteristics curve 0.86, 95% confidence interval 0.83‒0.89). The area under the receiver operating characteristics curve from the Global Registry of Acute Coronary Events risk score was 0.89. No significant differences were observed between both AUC values (P = .163). CONCLUSIONS AND IMPLICATIONS: The FRAIL scale independently predicted long-term outcomes in older patients with ACS. The predictive ability of this scale was comparable to the strongly recommended Global Registry of Acute Coronary Events risk score. Frailty assessment is mandatory for improving risk prediction in these complex patients.

Baseline ECG and Prognosis After Transcatheter Aortic Valve Implantation: The Role of Interatrial Block.

Background The clinical significance of conduction disturbances after transcatheter aortic valve implantation has been described; however, little is known about the influence of baseline ECGs in the prognosis of these patients. Our aim was to study the influence of baseline ECG parameters, including interatrial block (IAB), in the prognosis of patients treated with transcatheter aortic valve implantation. Methods and Results The BIT (Baseline Interatrial Block and Transcatheter Aortic Valve Implantation) registry included 2527 patients with aortic stenosis treated with transcatheter aortic valve implantation. A centralized analysis of baseline ECGs was performed. Patients were divided into 4 groups: normal P wave duration (<120 ms); partial IAB (P wave duration ≥120 ms, positive in the inferior leads); advanced IAB (P wave duration ≥120 ms, biphasic [+/-] morphology in the inferior leads); and nonsinus rhythm (atrial fibrillation/flutter and paced rhythm). The mean age of patients was 82.6±9.8 years and 1397 (55.3%) were women. A total of 960 patients (38.0%) had a normal P wave, 582 (23.0%) had partial IAB, 300 (11.9%) had advanced IAB, and 685 (27.1%) presented with nonsinus rhythm. Mean follow-up duration was 465±171 days. Advanced IAB was the only independent predictor of all-cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.10-1.98 [P=0.010]) and of the composite end point (death/stroke/new atrial fibrillation) (HR, 1.51; 95% CI, 1.17-1.94 [P=0.001]). Conclusions Baseline ECG characteristics influence the prognosis of patients with aortic stenosis treated with transcatheter aortic valve implantation. Advanced IAB is present in about an eighth of patients and is associated with all-cause death and the composite end point of death, stroke, and new atrial fibrillation during follow-up.

Optimized Preparation of Levofloxacin Loaded Polymeric Nanoparticles.

In this work, poly(lactic-co-glycolic acid) (PLGA) and chitosan (CS) nanoparticles were synthesized with the purpose of encapsulating levofloxacin (LEV). A thorough study has been carried out in order to optimize the preparation of LEV-loaded polymeric nanoparticles (NPs) suitable for parenteral administration. Changes in the preparation method, in the organic solvent nature, in the pH of the aqueous phase, or in the temperature were investigated. To the authors´ knowledge, a systematic study in order to improve the LEV nanocarrier characteristics and the yield of drug encapsulation has not been carried out to date. The physicochemical characterization of the NPs, their encapsulation efficiency (EE), and the in vitro release of LEV revealed that the best formulation was the emulsion-solvent evaporation method using dichloromethane as organic solvent, which renders suitable LEV loaded PLGA NPs. The morphology of these NPs was investigated using TEM. Their antimicrobial activities against several microorganisms were determined in vitro measuring the minimum inhibitory concentration (MIC). The results show that the use of these loaded LEV PLGA nanoparticles has the advantage of the slow release of the antibiotic, which would permit an increase in the time period between administrations as well as to decrease the side effects of the drug.

Prognosis of Patients With Severe Aortic Stenosis After the Decision to Perform an Intervention.

INTRODUCTION AND OBJECTIVES: Current therapeutic options for severe aortic stenosis (AS) include transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Our aim was to describe the prognosis of patients with severe AS after the decision to perform an intervention, to study the variables influencing their prognosis, and to describe the determinants of waiting time > 2 months. METHODS: Subanalysis of the IDEAS (Influence of the Severe Aortic Stenosis Diagnosis) registry in patients indicated for TAVI or SAVR. RESULTS: Of 726 patients with severe AS diagnosed in January 2014, the decision to perform an intervention was made in 300, who were included in the present study. The mean age was 74.0 ± 9.7 years. A total of 258 (86.0%) underwent an intervention: 59 TAVI and 199 SAVR. At the end of the year, 42 patients (14.0%) with an indication for an intervention did not receive it, either because they remained on the waiting list (34 patients) or died while waiting for the procedure (8 patients). Of the patients who died while on the waiting list, half did so in the first 100 days. The mean waiting time was 2.9 ± 1.6 for TAVI and 3.5 ± 0.2 months for SAVR (P = .03). The independent predictors of mortality were male sex (HR, 2.6; 95%CI, 1.1-6.0), moderate-severe mitral regurgitation (HR, 2.6; 95%CI, 1.5-4.5), reduced mobility (HR, 4.6; 95%CI, 1.7-12.6), and nonintervention (HR, 2.3; 95%CI, 1.02-5.03). CONCLUSIONS: Patients with severe aortic stenosis awaiting therapeutic procedures have a high mortality risk. Some clinical indicators predict a worse prognosis and suggest the need for early intervention.

Conservative management in very elderly patients with severe aortic stenosis: Time to change?

BACKGROUND: Despite current recommendations, a high percentage of patients with severe symptomatic aortic stenosis are managed conservatively. The aim of this study was to study symptomatic patients undergoing conservative management from the IDEAS registry, describing their baseline clinical characteristics, mortality, and the causes according to the reason for conservative management. METHODS: Consecutive patients with severe aortic stenosis diagnosed at 48 centers during January 2014 were included. Baseline clinical characteristics, echocardiographic data, Charlson index, and EuroSCORE-II were registered, including vital status and performance of valve intervention during one-year follow-up. For the purpose of this substudy we assessed symptomatic patients undergoing conservative management, including them in 5 groups according to the reason for performing conservative management [I: comorbidity/frailty (128, 43.8%); II: dementia 18 (6.2%); III: advanced age 34 (11.6%); IV: patients' refusal 62 (21.2%); and V: other reasons 50 (17.1%)]. RESULTS: We included 292 patients aged 81.5±9 years. Patients from group I had higher Charlson index (4±2.3), higher EuroSCORE-II (7.5±6), and a higher overall (42.2%) and non-cardiac mortality (16.4%) than the other groups. In contrast, patients from group III had fewer comorbidities, lower EuroSCORE-II (4±2.5), and low overall (20.6%) and non-cardiac mortality (5.9%). CONCLUSIONS: Patients with severe symptomatic aortic stenosis managed conservatively have different baseline characteristics and clinical course according to the reason for performing conservative management. A prospective assessment of comorbidity and other geriatric syndromes might contribute to improve therapeutic strategy in this clinical setting.

[Clinical predictors of left main coronary artery disease in high-risk patients with a first episode of non-ST-segment elevation acute coronary syndrome]. / Variables clínicas predictoras de enfermedad del tronco común en pacientes de alto riesgo con un primer episodio de síndrome coronario agudo sin elevación del segmento ST.

INTRODUCTION AND OBJECTIVES: Risk stratification in non-ST-elevation acute coronary syndrome makes use of clinical variables that can identify patients at an increased risk of complications. Our objective was to identify clinical variables that predict significant stenosis (i.e., >50%) of the left main coronary artery in high-risk patients who have had a first episode of non-ST-elevation acute coronary syndrome but who do not have a history of coronary artery disease. METHODS: The study included 102 high-risk patients with no history of coronary artery disease who were admitted because of non-ST-elevation acute coronary syndrome. All underwent coronary angiography. Patients were divided into two groups: those with significant left main coronary artery stenosis (n=14) and those without (n=88). RESULTS: Univariate analysis showed that the variables significantly associated with left main coronary artery stenosis were age >65 years (57.1% vs 15.9%, P=.002), diabetes mellitus (71.4% vs 33.0%, P=.006), chronic renal failure (28.6% vs 5.7%, P=.019), left heart failure (71.4% vs 6.8%, P< .0001), cardiogenic shock (21.4% vs 1.1%, P=.008), and a low left ventricular ejection fraction at admission (49.9% [14.7%] vs 58.8% [9.9%], P=.044). In the multivariate analysis, the only significant independent predictor of left main coronary artery disease was left heart failure. CONCLUSIONS: The presence of left heart failure at initial assessment of high-risk patients with non-ST-elevation acute coronary syndrome but without a history of coronary artery disease could be a useful predictor of significant left main coronary artery disease.

Binding of 12-s-12 dimeric surfactants to calf thymus DNA: Evaluation of the spacer length influence.

Several cationic dimeric surfactants have shown high affinity towards DNA. Bis-quaternary ammonium salts (m-s-m) have been the most common type of dimeric surfactants investigated and it is generally admitted that those that posses a short spacer (s≤3) show better efficiency to bind or compact DNA. However, experimental results in this work show that 12-s-12 surfactants with long spacers make the surfactant/ctDNA complexation more favorable than those with short spacers. A larger contribution of the hydrophobic interactions, which control the binding Gibbs energy, as well as a higher average charge of the surfactant molecules bound to the nucleic acid, which favors the electrostatic attractions, could explain the experimental observations. Dimeric surfactants with intermediate spacer length seem to be the less efficient for DNA binding.

Giant thrombus trapped in foramen ovale with pulmonary embolus and stroke.

We describe the case of a young man who, while he was in coma because of a traffic accident, had first a pulmonary embolus and immediately afterwards had a systemic (cerebral) embolus. A transesophageal echocardiographic image revealed a giant thrombi trapped in foramen ovale protruding in right and left ventricles, diagnosing, thus, a paradoxical embolism. The relationship between patent foramen ovale and pulmonary embolism has been reported in some series. Elevated right-chamber pressure caused by pulmonary hypertension could favor the establishment of a right-to-left shunt, causing, in some cases, paradoxical embolisms. We review the clinical implications.

[Post-anoxic encephalopathy after an episode of aborted sudden cardiac death]. / Encefalopatía postanoxémica tras un episodio de muerte súbita cardíaca recuperada.

INTRODUCTION AND OBJECTIVES: The presence of post-anoxic encephalopathy after an episode of aborted sudden cardiac death is a serious medical and social problem. PATIENTS AND METHOD: Of 193 patients admitted to the coronary unit during a 12-year period with aborted sudden cardiac death, 104 died (54%) and 89 survived the episode (46%). We compared the characteristics and 6-month prognosis between survivors according to the presence or absence of post-anoxic encephalopathy. RESULTS: Of 89 survivors, 38 patients were discharged alive with post-anoxic encephalopathy (42%) and 51 were discharged without neurological disturbances (58%). Patients with post-anoxic encephalopathy were older (65 13.6 vs. 59 12.9 years; p = 0.04). Mean time to care for cardiac arrest was 11.14.9 min in the post-anoxic encephalopathy group, versus 3.43 min (p < 0.01). The first documented rhythm was VF/VT in 57% and asystolia in 29% in the post-anoxic encephalopathy group, vs. 88% and 3% (p = 0.02). More than half (58%) of the patients in the post-anoxic encephalopathy group had coronary artery disease, vs. 49% (p = NS). Slightly more than half (52%) of the patients in the post-anoxic encephalopathy group had infectious complications, vs. 21% (p = 0.01). After 6 months of follow-up, mortality in patients discharged with post-anoxic encephalopathy was 62%, vs. 10% (p < 0.01); 21% of then showed significant functional improvement and 18% remained neurologically stable. CONCLUSIONS: Most patients admitted to a coronary unit with aborted sudden cardiac death died during hospitalization. Almost half of the survivors had post-anoxic encephalopathy at discharge; of these patients, 62% died within the following 6 months, and functional status improved only in a minority of them.